U Researchers Find Possible Autism Gene

U Researchers Find Possible Autism Gene

Feb 17, 2007 5:00 PM

SALT LAKE CITY - In an autism study of
unparalleled size and scope, the Autism Genome Project (AGP), a
worldwide consortium of leading researchers from the University of
Utah School of Medicine and 50 other institutions, has identified a
gene that may predispose people to autism.

The neurexin 1 gene belongs to a family of genes believed to be
important for developing contact and communication between neurons,
the nerve endings that allow various parts of the brain to send and
receive signals. AGP researchers identified the region that
includes a gene called neurexin 1 by combining two methods of
gathering genetic data-putting thousands of gene markers on
microchips and then analyzing the information to look for common
genetic traits of autism spectrum disorders and by searching for
variations or mutations in DNA coding contained in genes possibly
associated with the disorder. The group also identified a
previously unidentified region on chromosome 11 that may contain
another gene related to the mysterious brain disorder.

Funded by Autism Speaks, a national non-profit dedicated to
increasing awareness of autism and raising money to research the
disorder, and the National Institutes of Health, the preliminary
findings from the AGP's first phase were published online today by
Nature Genetics and also will be published in the
magazine's March print edition.

William M. McMahon, M.D., professor of psychiatry at the School
of Medicine and one of two Utah co-investigators in the study, said
identification of the chromosomal region containing neurexin 1 is
an encouraging step to understanding autism. Hilary Coon, Ph.D.,
research professor of psychiatry at the University, is the
project's other Utah co-investigator.

"This finding helps us focus our efforts on specific gene known
to play a role in brain development," Coon said. "We'll be using
some of these new techniques in our ongoing studies in other Utah
families."

Autism is a complex brain disorder that impairs social,
communicative, and behavioral development and often is
characterized by extreme behavior. A recent study from the U.S.
Centers for Disease Control looked at autism in 14 states,
including Utah, and found the disorder to be 20 times more
prevalent than two decades ago. Utah had the third highest rate of
autism-one in 133 children-of the 14 states surveyed.

The recent prevalence study showed autism to be 20 times more
frequent in Utah than was estimated in the UCLA-University of Utah
Autism Epidemiology Study conducted in the 1980s. McMahon and
others have begun contacting the adults who were children in the
study 20 years ago. "We believe many of the children who did not
meet autism diagnostic criteria 20 years ago, may meet current
criteria," McMahon said. "This may help us understand why autism
prevalence is higher and we'd like to test genes such as neurexin 1
in these adults."

People who wish to volunteer for this and other genetic studies
can call the Utah Autism Center at (801) 585-9098.

In 2002, more than 120 AGP researchers from 19 countries began
gathering DNA samples from autistic individuals in nearly 1,200
families. The DNA was placed on microchips, enabling scientists to
compare 10,000 DNA markers and identify chromosome regions shared
among people with autism, a technique called linkage. Researchers
also scanned DNA from these families to look for copy number
variations (CNV)-additions or deletions in genetic coding that may
well be linked to autism and other disorders and diseases.

The goal was to identify genes that make people susceptible to
autism. By combining information from the gene chip technology and
CNV, added to the unprecedented statistical power provided by the
uniquely large genetic sample, the researchers identified neurexin
1 as a possible susceptibility gene. Other genes in that region of
chromosome 11, and throughout the entire genome, also may make good
candidates for susceptibility genes and will be examined in the
studys second phase.

Andy Shih, Autism Speaks chief science officer, said the
innovative combination of gene chips and CNV were critical in
focusing on neurexin 1 and potentially other genes that may make
people susceptible to autism. Identifying these genes can lead to
breakthroughs in diagnosing and treating patients and in supporting
families.

"By combining cutting-edge CNV analysis with more traditional
linkage and association (analyses), the scientists now have a
promising new framework to look for autism susceptibility genes,"
Shih said. "These exciting findings from the AGP linkage scan
confirm the value and contribution of multidisciplinary
collaboration to advancing autism research."

In phase two of the AGP, beginning soon, researchers will expand
use of gene chip technology to search the genome for new genetic
markers of autism, as well as search chromosomes for copy number
variations associated with autism spectrum disorders. To do this,
the AGP will use high throughput DNA sequencing, a technique that
allows researchers to look at vast numbers of DNA sequences to
pinpoint underlying changes in autism susceptibility genes.